Faculty of Medicine, Pharmacology, University of Helsinki, Helsinki, Finland.
Faculty of Medicine, Human Microbiome Research Program, University of Helsinki, Helsinki, Finland.
J Physiol Pharmacol. 2024 Apr;75(2):185-194. doi: 10.26402/jpp.2024.2.07. Epub 2024 May 6.
We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the physiological factor which stimulates aldosterone synthesis in the adrenal glands. We have recently demonstrated that Ang II stimulates aldosterone synthesis also in mouse colon. Here, we conducted a 75-min ex vivo incubation of murine colonic tissue and evaluated the effects of three other Ang peptides, Ang I (1 μM), Ang III (0.1 μM) and Ang (1-7) (0.1 μM) on aldosterone synthesis. As a possible mechanism, their effects on tissue levels of the rate-limiting enzyme, aldosterone synthase (CYP11B2) were measured by ELISA and Western blot. Ang III significantly elevated the amount of tissue CYP11B2 protein in colon. The values of released aldosterone in colon tissue incubation were increased over the control in the presence of Ang I, II or III, however, being statistically non-significant. In Western blot analysis, the values of tissue CYP11B2 protein content were elevated by Ang I and II. Ang (1-7) alone in colon did not influence CYP11B2 protein levels in the incubation experiment but showed higher aldosterone release without statistical significance. Ang (1-7) showed an antagonistic effect towards Ang II in release of aldosterone in adrenal gland. An overall estimation of a single peptide (three measured variables), the results were always in an increasing direction. The responses of aldosterone synthesis to high levels of glucose (44 mM) and potassium (18.8 mM) as physiological stimulators in vivo were investigated in the colon incubation. Glucose, equal to four times the concentration of the control buffer in the incubation, showed higher values of aldosterone release in colon than control without statistical significance similarly to the effect seen in adrenal glands. Increasing the concentration of potassium in the incubation buffer exerted no effect on colonic aldosterone production. Intriguingly, no correlation was found between aldosterone release and the tissue CYP11B2 protein content in colon. In summary, the response of colonic aldosterone synthesis to different Ang peptides resembles, but is not identical to, the situation in the adrenal glands.
我们之前描述过小鼠结肠中的局部醛固酮合成。在肾素-血管紧张素-醛固酮系统（RAAS）中，血管紧张素 II（Ang II）肽是刺激肾上腺醛固酮合成的生理因子。我们最近证明 Ang II 也刺激小鼠结肠中的醛固酮合成。在这里，我们对小鼠结肠组织进行了 75 分钟的离体孵育，并评估了另外三种 Ang 肽，即 Ang I（1 μM）、Ang III（0.1 μM）和 Ang（1-7）（0.1 μM）对醛固酮合成的影响。作为一种可能的机制，通过 ELISA 和 Western blot 测量了它们对组织中限速酶醛固酮合酶（CYP11B2）水平的影响。Ang III 显著增加了结肠组织中 CYP11B2 蛋白的量。在存在 Ang I、II 或 III 的情况下，与对照相比，结肠组织孵育中释放的醛固酮量增加，但统计学上无显著性差异。在 Western blot 分析中，Ang I 和 II 均升高了组织 CYP11B2 蛋白含量。Ang（1-7）单独在结肠中并不影响孵育实验中 CYP11B2 蛋白水平，但显示出更高的醛固酮释放，无统计学意义。Ang（1-7）在肾上腺中对 Ang II 释放醛固酮表现出拮抗作用。对单个肽（三个测量变量）的总体评估，结果始终呈上升趋势。在结肠孵育中，研究了高浓度葡萄糖（44 mM）和钾（18.8 mM）作为体内生理刺激物对醛固酮合成的反应。葡萄糖在孵育中的浓度是对照缓冲液的四倍，在结肠中的释放值高于对照，但无统计学意义，与肾上腺中的作用相似。增加孵育缓冲液中钾的浓度对结肠中醛固酮的产生没有影响。有趣的是，在结肠中，醛固酮的释放与组织 CYP11B2 蛋白含量之间没有发现相关性。总之，不同 Ang 肽对结肠醛固酮合成的反应类似于但不完全等同于肾上腺中的情况。
